A major feature that eventually allows a tumor to kill the patient is the diversity of the tumor's cells. How this heterogeneity emerges and how it is maintained is not entirely clear. One of the factors that can contribute to tumor cell diversity is cell fusion. Cell fusion is a tightly controlled, though poorly understood, process that is normally restricted in the human body to only a few cell types. However, the ability to fuse appears to be common for tumor cells and has been implicated in progression of experimental tumors. How tumor cells acquire the propensity to fuse is unknown, and tractable models to study this phenomenon are not available. We have found that the oncogenes myc and E1A render normal human cells fusogenic, an observation that suggests that the ability to fuse is a part of oncogenic transformation. To test this hypothesis, we propose to identify molecules that mediate oncogene-induced cell fusion and to investigate whether expression or regulation of these molecules is affected in tumor cells. The observation that the ability to fuse can be conferred to normal cells by oncogenes offers a tractable experimental system to investigate this phenomenon. Our experience with using this system to dissect the molecular mechanisms of oncogene induced apoptosis will help us significantly in achieving our goals, which are: (i) to identify the activity that mediates oncogene-induced cell fusion; (ii) to investigate whether cell fusion contributes to cancer development in vivo. These studies will advance our understanding of how oncogenes transform normal cells and may identify new mechanisms that increase the heterogeneity of tumors.